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Evaluation of treatment outcomes in ductal and intraductal prostate cancer: Insights from the National Cancer Database.
5122 Background: Ductal and intraductal Prostate carcinoma (DPC) are rare and aggressive histological subtypes of prostate cancer. Based on risk stratification, treatment strategies for localized DPC include radical prostatectomy (RP), radiation with androgen deprivation therapy (RT±ADT), and observation. However, literature on outcomes across various treatment modalities in DPC is limited. Understanding the impact of these approaches on survival is important for strategizing DPC management. We used the national cancer database to evaluate the survival outcomes with various treatment strategies in DPC. Methods: Our study focused on patients diagnosed with localized DPC between 2004 and 2020. Patients were stratified into three arms: RP arm included those who underwent RP with or without adjuvant therapy, RT +/- ADT arm included patients who underwent RT with or without ADT, and observation arm included those who had no treatment. We performed Multivariate Cox regression analysis adjusting for age, race, NCCN risk classification, comorbidities, socioeconomic factors, and facility type. We also conducted Kaplan-Meier analysis to evaluate Overall Survival (OS) across the treatment arms. Results: We analyzed 2,650 patients with localized DPC. 1586(59.9%) underwent RP, 785(29.6%) underwent RT±ADT, and 279(10.5%) were under observation. 2-year OS for RP, RT±ADT, and observation were 98%, 94% and 78% respectively (p<0.001). Similarly, 5-year OS was 92%, 81%, and 54%, respectively (p<0.001). Multivariate Cox regression showed that RT+ADT was associated with increased mortality compared to RP (HR: 2.27; p<0.001). 2-year OS for patients with PSA ≤4 ng/dL and >4 ng/dL was 89.9% and 97.2%, respectively. Similarly, 5-year OS were 75.8% and 88.8%, respectively. Multivariate Cox regression showed that PSA <=4 was associated with an increased risk of mortality compared with PSA >4 (HR: 1.27; p<0.05). Conclusions: Surgery offers better survival than radiation in localized DPC. The association of low PSA with worse prognosis could be due to dedifferentiation-driven aggressiveness. Therefore, further evaluation of treatment strategies for DPC is warranted.
Predictive value of genomic mutation signatures and tumor mutational burden for induction immunochemotherapy in locally advanced squamous cell carcinoma of the oropharynx, larynx, and hypopharynx.
e14592 Background: The predictive role of programmed death-ligand 1 (PD-L1) expression in patients (pts) with head and neck squamous cell carcinoma (HNSCC) is imperfect: clinically meaningful responses are observed in a subset of pts with low PD-L1 expression, highlighting the need to identify additional biomarkers. This study evaluated the association of genomic mutations and tumor mutational burden (TMB) with the efficacy of induction immunochemotherapy (ICT) in HNSCC. Methods: Molecular genetic analysis was performed on tumor biopsies from pts enrolled in a prospective phase II study of ICT with pembrolizumab plus platinum-based chemotherapy for locally advanced HNSCC between 2022 and 2024 (NCT05551767). The clinical relevance of genomic alterations was classified according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). The association of the spectrum of somatic mutations and copy number alterations with objective response rate (ORR) and progression-free survival (PFS) on ICT was analyzed. TMB (mutations per megabase, mut/Mb) and microsatellite status were assessed using next-generation sequencing. Results: A total of 64 tumor samples were analyzed. The most frequently mutated genes were TP53 (n = 18, 36%), SDHA (n = 11, 22%), CDKN2A (n = 6, 12%), PIK3CA (n = 6, 12%), NOTCH1 (n = 6, 12%), and NTRK3 (n = 6, 12%). Copy number alterations were dominated by amplifications of FGF19 (n = 16, 32%), FGF4 (n = 16, 32%), FGF3 (n = 16, 32%), and CCND1 (n = 15, 30%). Four tumors (6%) had TMB ≥10 mut/Mb; no microsatellite instability was detected. TMB ≥10 mut/Mb was the only biomarker meeting ESCAT tier I evidence. All 4 pts with TMB ≥10 mut/Mb achieved a partial response to ICT; only 1 pt experienced disease progression within 12 months after treatment initiation, while 3 pts remained progression-free with follow-up of 20–27 months. Among 58 evaluable pts with TMB < 10 mut/Mb, 37 (63.8%) achieved an objective response after 3 cycles of ICT. There was no statistically significant difference in ORR between TMB ≥10 mut/Mb and < 10 mut/Mb cohorts (p = 0.35). High TMB also did not significantly impact PFS (hazard ratio 0.46, 95% confidence interval 0.06–3.47, p = 0.45). Conclusions: The high clinical activity of ICT observed in this cohort cannot be explained by TMB as a predictive biomarker. These findings suggest that alternative biomarkers are required to better predict benefit from induction ICT in locally advanced HNSCC.
Olanzapine versus aprepitant based triple antiemetic regimens for the prevention of chemotherapy-induced nausea and vomiting in adult patients receiving highly emetogenic chemotherapy: A systematic review and meta-analysis.
e24088 Background: Chemotherapy-induced nausea and vomiting (CINV) significantly affects treatment tolerance and quality of life. ASCO guidelines recommend a NK-1 receptor antagonist with a 5-HT3 receptor antagonist and corticosteroid for patients receiving highly emetogenic chemotherapy (HEC). Olanzapine has emerged as an alternative antiemetic, with evidence suggesting noninferiority in triple regimens. Given its favorable cost profile, we performed a pooled analysis comparing olanzapine- versus aprepitant-based triple antiemetic regimens for CINV prevention. Methods: This PRISMA-compliant review was prospectively registered in PROSPERO (CRD420261284983). Five databases were systematically searched to identify studies comparing olanzapine (OLZ) versus aprepitant (APR) based triple antiemetic regimens. The primary endpoint was complete response (CR) for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in adult patients receiving HEC. Statistical analyses were performed in R (version 2025.05.0+496; Posit). Results: 13 studies were included in the final synthesis, comprising 1,557 patients (OLZ: n = 779; APR: n = 788). CR was comparable between groups (RR 1.02, 95% CI 0.95–1.09; I² = 55.8%). Exclusion of Mehta et al. (2017) reduced heterogeneity to zero (I² = 0%). In the acute phase ( < 24 h), CR was also similar between OLZ and APR (RR 1.09, 95% CI 0.98–1.20; I² = 82.7%); however, OLZ demonstrated superior CR in the 10-mg dose subgroup (RR 1.08, 95% CI 1.03–1.14; I² = 74%). For delayed-phase CR (24-120 h), the pooled effect estimate was RR 1.11 (95% CI 0.98–1.27; I² = 84.3%). Control of nausea was significantly improved in the OLZ group compared with APR (RR 1.19, 95% CI 1.01–1.40; I² = 72.8%), particularly in anthracycline–cyclophosphamide–based regimens (RR 1.30, 95% CI 1.09–1.54; I² = 62.9%) and the 10-mg OLZ dose subgroup (RR 1.22, 95% CI 1.01–1.49; I² = 75.2%). Nausea control was also superior in both the acute phase (RR 1.13, 95% CI 1.01–1.27; I² = 76.5%) and the delayed phase (RR 1.31, 95% CI 1.05–1.65; I² = 93.3%). Control of vomiting was comparable between OLZ and APR (RR 0.99, 95% CI 0.92–1.07; I² = 0%), with no significant differences observed in the acute ( < 24 h) phase (RR 1.03, 95% CI 0.97–1.10; I² = 49%) or the delayed (24–120 h) phase (RR 1.00, 95% CI 0.97–1.04; I² = 0%). Conclusions: OLZ-based triple antiemetic regimens provide comparable CR and vomiting control to APR, with superior nausea control, particularly in anthracycline–cyclophosphamide regimens and at the 10-mg dose.
First-line treatment patterns of advanced non–small cell lung cancer in patients with and without pre-existing autoimmune diseases.
e20626 Background: Immune checkpoint inhibitors (ICIs) are established first-line therapies for advanced NSCLC (aNSCLC). However, ICIs carry a risk of immune-mediated adverse events, and patients (pts) with autoimmune diseases (AID) may be at heightened risk of disease flare or new symptoms of autoimmunity. As a result, pts with pre-existing AIDs have been excluded from clinical trials, and their treatment patterns in the real world are not well-described. This study aimed to elucidate drug utilization patterns in first-line (1L)-treated aNSCLC pts, with and without pre-existing AIDs. Methods: Using the Optum Enriched Oncology dataset, pts (≥18 years) with aNSCLC (stage IIIB/C or IV) treated with either ICIs (alone or in combination with other therapies, including chemotherapy) or chemotherapy alone, not restricted to platinum-containing agents, in the 1L setting between 10 May 2017 and 1 March 2025 were identified. Pts with prior receipt of a targeted therapy for NSCLC or an actionable mutation were excluded. Pre-existing AID was operationalized using either ICD-10 codes or NLP-derived terms on or before (≤365 days) the date of 1L treatment initiation, and further stratified into high- and low-risk AIDs based on the risk of flares associated with the specific underlying AID. Results: Clinical and demographic characteristics were comparable between pts with AID (N = 779) and those without AID (N = 6,186), except for sex, where a higher proportion of females was observed in the AID group (54% vs. 45%). Among pts without AID, 62.7% received 1L ICI treatment and 37.3% received chemotherapy, which remained relatively stable over time (Table). Pts with low-risk AIDs showed similar proportions, with 62.2% receiving ICIs and 37.8% receiving chemotherapy. In contrast, a lower proportion of pts with high-risk AIDs received an ICI (51.6%). Utilization rates were heterogenous across specific AIDs, and certain high-risk AIDs, such as Crohn’s disease (41.7%) and multiple sclerosis (25.0%), show markedly lower rates of ICI utilization compared to the overall proportion observed among all high-risk pts. Conclusions: Similar patterns of predominant ICI utilization were observed among pts without AID and those with low-risk AID. In contrast, fewer pts with high-risk AID received ICIs, implying that risk status in these pts may be guiding treatment decisions. However, approximately half of the high-risk pts are still treated with ICIs, suggesting that prescribers are often comfortable using ICIs in pts with pre-existing AID. Temporal trends for 1L treatment for NSCLC, by AID status. AID No AID Year N Chemotherapy ICI N Chemotherapy ICI 2017 74 66% 34% 561 60% 40% 2018 105 46% 54% 888 46% 54% 2019 107 41% 59% 935 33% 67% 2020 98 44% 56% 914 34% 66% 2021 92 50% 50% 858 34% 66% 2022 90 43% 57% 675 33% 67% 2023 88 38% 63% 653 30% 70% 2024 110 34% 66% 603 33% 67% 2025 15 47% 53% 99 37% 63%
Economic evaluation of a designated oncology pharmacist in hemato-oncology outpatient care: A randomized clinical trial.
11063 Background: Adverse drug reactions (ADRs) and medication errors are major contributors to morbidity and healthcare utilization in hemato-oncology. In a randomized clinical trial, we previously demonstrated that integrating a designated oncology pharmacist significantly reduced ADRs and intercepted potentially serious medication errors. The economic value of this intervention has not yet been established. Methods: We conducted a trial-based cost-effectiveness analysis alongside a single-center randomized clinical trial (n=182), in which adult patients with hematologic malignancies were randomized 1:1 to comprehensive pharmaceutical care delivered by a designated oncology pharmacist versus standard care. Patients were followed for 5 months (4-month intervention plus 1-month follow-up). The primary economic outcome was incremental cost per ADR avoided; secondary outcomes included cost per emergency department visit and hospitalization avoided. The analysis was conducted from the public healthcare system perspective and included only the pharmacist program cost, estimated at $105 per patient over the 5-month study period. Incremental cost-effectiveness ratios (ICERs) were calculated using absolute risk reduction, with uncertainty assessed by nonparametric bootstrap resampling (5,000 replications). Costs are reported in 2022 USD. Results: ADRs occurred in 47.3% of control patients compared with 23.1% of intervention patients, corresponding to an absolute risk reduction of 24.2% and a number needed to treat of 4.1. The ICER was $434 per ADR avoided (bootstrap 95% CI: $281–$956), with a >99.9% probability that the intervention reduced ADRs. Secondary outcomes also favored the intervention: emergency department visits (37.4% vs 28.6%; ICER $1,194 per visit avoided) and hospitalizations (28.6% vs 23.1%; ICER $1,911 per hospitalization avoided). In addition, the pharmacist intercepted 287 medication errors in real time, including 13 potentially severe errors, with a physician acceptance rate of 94.8%. Conclusions: This economic evaluation demonstrates that integrating a designated oncology pharmacist in hemato-oncology outpatient care is a cost-effective strategy for preventing ADRs and reducing acute healthcare utilization. These findings support broader implementation of oncology pharmacists as a high-value patient safety intervention.
Anthracycline- and immunotherapy-free neoadjuvant chemotherapy versus KEYNOTE-522 regimen in early-stage triple-negative breast cancer.
e12647 Background: Neoadjuvant chemotherapy (NACT) is standard of care in early-stage triple-negative breast cancer (TNBC), with pathologic complete response (pCR) as a surrogate endpoint. KEYNOTE-522 demonstrated improved outcomes with pembrolizumab added to anthracycline–taxane–platinum chemotherapy. However, the comparative benefit of this approach versus anthracycline- and immunotherapy-free regimens remains unclear. Methods: This single-center observational study included consecutive patients with stage II–III TNBC treated with NACT between 2021 and 2024. One group received carboplatin–docetaxel (CbT) plus pegfilgrastim, and the other received the KEYNOTE-522 regimen. Pathologic response was assessed using pCR (RCB 0) and RCB 0–1. Radiologic response, grade ≥3 toxicity, and treatment discontinuation were analyzed. Results: Seventy-four patients were included; 36 received pembrolizumab plus chemotherapy and 38 received CbT. Median age was 53 years; most patients had ECOG PS 0–1. Pathologic response was evaluable in 63 patients. Overall pCR rate was 61.9%. pCR was significantly higher with pembrolizumab compared with chemotherapy alone (79.2% vs 51.3%; OR 3.61, 95% CI 1.12–11.61; p = 0.027). Stage-stratified analysis showed higher pCR rates with pembrolizumab across both stage II and III disease, with the greatest absolute benefit in stage II. A higher rate of favorable pathologic response (RCB 0–1) was also observed with pembrolizumab (79.2% vs 56.4%; OR 2.94). Complete radiologic response was similar between groups (50.0% vs 48.7%). Grade ≥3 adverse events occurred more frequently with pembrolizumab (41.7% vs 28.2%; OR 1.82), mainly myelotoxicity and asthenia, but toxicity was manageable with low treatment discontinuation rates (8.3% vs 7.7%; OR 1.09). No treatment-related deaths or severe immune-related adverse events were observed. At data cutoff, follow-up was short and no significant differences in disease-free or overall survival were detected. Conclusions: In this real-world cohort, pembrolizumab added to neoadjuvant chemotherapy significantly increased pCR and RCB 0–1 rates with acceptable safety. Platinum-based anthracycline- and immunotherapy-free chemotherapy showed encouraging activity and may represent a valid alternative for selected patients unfit for standard regimens. These findings warrant validation in prospective studies. pCR by treatment group (χ² test, p = 0.027). Carboplatine- Docetaxel Pembrolizumab- Carboplatine - Docetaxel Total pCR NO 48,7 % (n 19) 20,8 (n 5) 38,1% YES 51,3% (n 39) 79,2 % (n 24) 61,9%
Risk of renal adverse events (RE-AE) and electrolyte changes with immunotherapy (IT) in a real-world cohort.
11149 Background: IT is used across multiple tumor types but is linked to immune-related AE (irAE), including RE-AEs. Acute kidney injury (AKI) is the most common renal irAE (1–2%); however, real-world comparative data on RE-AE & electrolyte trends across tumor types remain limited. We evaluated RE-AE incidence & longitudinal electrolyte & urine trends following IT. Methods: We conducted a retrospective cohort study of 5,556 adult cancer patients treated at Cleveland Clinic Ohio between 2010–2022. Included cancers were advanced-stage (III–IV) bladder, endometrial, esophageal, gastric, head & neck, renal, & lung cancers (NSCLC/SCLC), & metastatic melanoma. We compared IT (± chemo/radiation) vs non-IT regimens. Follow-up began at systemic therapy initiation & continued until RE-AE, death, or last encounter. Outcomes included AKI, AKI progressing to chronic kidney disease (CKD), & clinically significant proteinuria. Poisson regression estimated incidence rates, Kaplan–Meier methods cumulative incidence (CIR), & time-dependent Cox models assessed risk with IT as a time-varying exposure. Longitudinal serum electrolytes & urine parameters were extracted electronically & analyzed via mixed-effects & generalized linear models over a one-year post-initiation period. Results: Among the cohort, 1,291 (23%) received first-line IT & 4,265 (77%) later-line IT. Median age was 66 years; 38% were female. During median follow-up of 14 months (CI 6-34), 195 RE-AEs occurred (IT: 46; non-IT: 149). The incidence rates per 100 person years were 0.18 (0.13, 0.24) in IT group & 0.13 (0.11, 0.15) in non-IT group. 2-year CIR was 4.6% with IT & 3.9% without IT (P = 0.6). Adjusted time-dependent Cox models demonstrated no significantly increased risk for AKI, CKD, or composite RE-AEs associated with IT exposure: [AKI HR 0.99 (0.7–1.5); CKD HR 1.5 (0.97–2.4); RE-AE HR 1.3 (0.9–1.7)]. Most RE-AEs were CTCAE grade II–III. Immunomodulatory therapy was used in 15%, primarily steroids, with a 50% response rate. Longitudinal analyses showed IT was associated with higher mean CO₂ & calcium compared with non-IT (P < 0.05), but not other labs (Table 1). While on therapy, IT was associated with lower urine pH (β = -0.37, CI -0.69 -0.04) but no other UA parameter changes were noted. Conclusions: In this large real-world cohort, IT was not associated with an increased incidence of RE-AE compared with non-IT therapy, suggesting that stringent trial exclusion criteria for baseline renal impairment may be unnecessarily restrictive. IT was associated with statistically significant changes in calcium, CO₂, & urine pH, the clinical significance of which remains uncertain. Laboratory parameter Estimate 95% CI Sodium 0.14 -0.04 – 0.32 Potassium 0.02 -0.001 – 0.04 BUN -0.03 -0.59 – 0.54 Creatinine 0.02 -0.003 – 0.05 CO2/ Bicarbonate 0.16 0.001 – 0.32 Calcium 0.10 0.067 – 0.14 Chloride 0.18 -0.038 – 0.4 GFR -1.59 -4.73 – 1.55 Phosphorus -0.11 -0.25 – 0.04
Trends in mortality due to lung cancer and infectious respiratory diseases in US from 1999 to 2020: A CDC WONDER analysis.
e20117 Background: Respiratory illnesses, especially infections and lung cancer, are among the deadliest health issues worldwide. Research suggests that lung infections not only occur alongside cancer but may also contribute to its development by weakening the immune system and causing chronic inflammation. These risks vary depending on geography, socioeconomic factors, and access to care, highlighting the need for targeted and equitable public health strategies. Methods: A retrospective analysis was conducted using CDC WONDER data from 1999–2020. Deaths were included if both lung cancer (ICD-10: C34) and infectious respiratory diseases (ICD-10: J09–J18) were listed. Adults aged 25–80 years were analyzed by age, sex, race/ethnicity, region, urbanization and place of death. Age-adjusted mortality rates (AAMRs) per 100,000 population with 95% confidence intervals (CIs) were calculated. Joinpoint regression was used to analyze trends and compute annual (APC) and average annual percent changes (AAPC). Results: From 1999 to 2020, a total of 194,541 adult deaths were identified, corresponding to an overall AAMR of 4.04 per 100,000. Over the study period, mortality demonstrated a sustained decline, with AAMR decreasing from 5.90 in 1999 to 3.16 in 2020, and the most pronounced reduction observed between 2006 and 2009. The majority of deaths occurred in hospital settings (75.3%), followed by home (9.4%) and nursing home (8.7%) settings. Mortality burden was higher among men, who accounted for 118,480 deaths and had a significantly higher AAMR (5.65) compared with women (2.82). Racial and ethnic disparities were observed as Non-Hispanic (NH) Black individuals exhibited the highest AAMR (4.65), followed by NH White (4.01), NH Asian or Pacific Islander (3.16), and NH American Indian or Alaska Native populations (3.03), while Hispanic individuals had the lowest mortality rate (2.01). Although mortality decreased across all racial and ethnic groups, the rate of decline slowed or plateaued after 2009. West Virginia and Kentucky demonstrated the highest state-level AAMRs, whereas Utah and Colorado had the lowest. Regionally, mortality was highest in the South (AAMR: 4.31), followed by the Midwest (4.10) and Northeast (3.90), with the West exhibiting the lowest mortality (3.60). Additionally, nonmetropolitan areas experienced consistently higher mortality rates (12.63) than metropolitan areas (10.64) and showed slower improvements over time. Conclusions: Lung cancer mortality in the U.S. steadily declined from 1999 to 2020, but not all groups benefited equally. Men, NH Black individuals, rural residents, and those in South region experienced higher death rates and slower improvement, pointing to persistent health inequities.
Cancer cachexia staging as a predictor of treatment receipt and survival in pancreatic ductal adenocarcinoma.
e16354 Background: Many individuals with pancreatic ductal adenocarcinoma (PDAC) do not receive treatment or enroll in clinical trials, and there is limited literature to guide treatment selection. Given the association between cancer cachexia and poor outcomes, we evaluated whether the University of Texas (UT) Cancer Cachexia Staging System (CCSS) or other clinical variables could predict receipt of treatment and overall survival in PDAC patients. Methods: We conducted a retrospective cohort study of 66 adults diagnosed with PDAC at a single tertiary care center from 2022–2024. Patients were categorized by receipt of systemic therapy. Clinical, demographic, and disease-related variables were compared between treated and untreated groups. UT CCSS scores were calculated for all patients. Descriptive statistics were summarized using medians, interquartile ranges, and percentages. Group comparisons used Fisher’s exact test (p < 0.05), and OS was analyzed using a Cox proportional hazards model. All statistical analyses were conducted using GraphPad Prism version 10.2.2. Results: Overall, 50 patients (75%) received systemic chemotherapy and 16 (25%) did not. Among untreated patients, UT CCSS stages were I (n = 3), II (n = 9), and III (n = 4), compared with stage I (n = 20), II (n = 27), and III (n = 3) among treated patients. Median CA 19-9 levels were 175 (range 5–47,242) in the untreated group and 216 (range 3–574,876) in the treated group. Patients receiving chemotherapy more frequently had advanced TNM stage (III/IV) and higher UT CCSS stage (II/III), while lower TNM stage (I/II) was more common among patients with UT CCSS stage I. Metastatic presentation was 62.5% in the untreated group versus 34% in the treated group. The treated group had a higher percentage (88%) of weight loss. Survival analysis comparing UT CCSS stage I versus II/III demonstrated improved survival in stage I patients, with 85% alive versus 73% at a median follow-up of 10.9 and 11.7 months, respectively (hazard ratio 0.52, 95% CI 0.16–1.73). Conclusions: Among patients with PDAC receiving systemic therapy, advanced cachexia (UT CCSS stage II/III) was associated with worse survival compared with stage I. Use of the UT CCSS may help guide selection of patients for chemotherapy versus best supportive care. Study limitations include a small number of untreated patients and limited follow-up. Prospective validation of the UT CCSS in PDAC treatment decision-making is warranted.
Prognostic heterogeneity of metastatic patterns in prostate cancer relative to bone-only disease.
e17108 Background: Metastatic prostate cancer exhibits heterogeneous patterns of spread, but prior studies have not distinguished distant lymph node from visceral organ metastases when characterizing non-bone disease. Methods: Using the National Cancer Database (2016-2022), 56,112 patients with documented metastatic prostate cancer at diagnosis were identified. Patients were classified into five mutually exclusive groups based on sites of metastatic involvement: bone-only, distant lymph node-only, visceral organ-only (liver, lung, or brain), distant lymph node plus visceral organs without bone, and bone plus any non-bone site. Multivariable Cox proportional hazards regression was used to estimate associations between metastatic pattern and overall survival, adjusting for demographics, comorbidities, tumor characteristics, and treatment facility; complete-case analysis was performed. Results: Among 56,112 patients, 64% had bone-only metastases, 6% distant lymph node-only, 3% visceral organ-only, 1% distant lymph node plus visceral organs, and 26% bone plus non-bone metastases. Median follow-up ranged from 22 to 32 months across groups. Compared to bone-only disease (reference; 53% mortality), distant lymph node-only metastases conferred substantially lower mortality (36% deaths; adjusted hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.60-0.68), while visceral organ-only metastases showed similar survival to bone-only disease (56% deaths; HR 1.06, 95% CI 1.00-1.13, p = 0.09). Patients with bone plus non-bone metastases had the highest mortality (61% deaths; HR 1.34, 95% CI 1.31-1.38). Among 6,853 patients with non-bone-only disease, 60% had isolated distant lymph node involvement, explaining the apparent survival advantage of aggregated non-bone disease. These associations persisted after adjusting for treatments received and were consistent across major histology subtypes. Conclusions: Distant lymph node and visceral organ metastases represent distinct prognostic entities in metastatic prostate cancer. Distinguishing these patterns enables more precise risk stratification relative to traditional bone-only classification and may inform treatment selection. Adjusted hazard ratios for overall survival by metastatic phenotype. Metastatic phenotype Adjusted HR 95% CI Bone-only (reference) 1 — Distant LN-only 0.64 0.60–0.68 Visceral-only 1.06 1.00–1.13 LN + visceral (no bone) 1.18 1.08–1.29 Bone + non-bone 1.34 1.31–1.38 Hazard ratios derived from multivariable Cox proportional hazards models adjusted for demographics, comorbidity burden, tumor characteristics, year of diagnosis, and treatment facility type. The better prognosis of isolated distant lymph node metastases warrants prospective validation and consideration in clinical trial design.
De-escalation in the elderly: Adjuvant fluoropyrimidine monotherapy vs oxaliplatin-based regimens in stage 3 colon cancer patients aged ≥ 75.
e15646 Background: Addition of oxaliplatin to adjuvant fluoropyrimidine therapy (FOLFOX/CAPOX) is the established standard of care for stage III colon cancer but its benefit in patients ≥75 years remains controversial, as pivotal trials (MOSAIC, NSABP C-07) largely underrepresented this demographic. Pooled analyses (ACCENT database) suggest that survival benefits of oxaliplatin diminish and toxicity increase with age. We aimed to evaluate the therapeutic value and safety burden of adding oxaliplatin to adjuvant therapy in elderly patients. Methods: Using TriNetX global network, we identified patients ≥75 years with resected stage III colon cancer who initiated adjuvant chemotherapy within 4 months of colectomy. Two cohorts were defined: Monotherapy (fluorouracil/capecitabine; n = 262) and Combination Therapy (fluorouracil/capecitabine plus oxaliplatin; n = 427). 1:1 propensity score matching (PSM) was performed for demographics, comorbidities (CKD, HTN, DM, COPD, HF, IHD), markers of geriatric frailty (wheelchair/oxygen use, age-related debility, cachexia, reduced mobility, and need for assistance), disease severity (intestinal obstruction at diagnosis) and baseline neuropathy. Outcomes were 5 year Overall Survival (OS), 5-year incidence of metastases; 180 day health care utilization (HCU) and drug induced polyneuropathy rates and 90-day neutropenia and thrombocytopenia (grade 2); calculated from first chemotherapy. Results: Before matching, combination cohort was significantly younger with fewer comorbidities and baseline neuropathy. After matching (n = 195/arm), 5 year OS was numerically higher in the combination therapy cohort but did not reach statistical significance compared to monotherapy (74.3% vs 61.9%; p = 0.08). Addition of oxaliplatin was associated with higher 180 day health care utilization (42.1% vs 31.8%; HR 0.756, 95% CI 0.58–0.98; p = 0.036), reflecting increased toxicity without significant survival gain. Conclusions: In patients ≥75 with stage III colon cancer, addition of oxaliplatin to adjuvant therapy increases the burden of health care utilization without adding a statistically significant survival benefit. These real world findings align with ACCENT pooled analyses and support treatment de-escalation as fluoropyrimidine monotherapy preserves efficacy while minimizing toxicity. Priority should be given to quality of life and geriatric assessment when selecting adjuvant regimens for the oldest old. Outcome Monotherapy cohort (n= 195) Combination therapy cohort (n= 195) Hazard Ratio/ Risk Ratio (95% CI) P-value 5 year Survival Probability 61.91% 74.53% - 0.08 5 year Metastasis 20.21% 21.88% 0.92 (0.66, 1.36) 0.69 HCU 31.8% 42.1% 0.76 (0.58, 0.98) 0.036 Neutropenia 9.23% 23.08% 0.4 (0.24,0.67) <0.001 Thrombocytopenia 9.23% 33.33% 0.277 (0.17,0.45) <0.001 Polyneuropathy 8.8% 23.9% 0.37 (0.22,0.63) <0.001
Patient-reported outcomes for identification of distinct tolerance phenotypes with differential survival impact under osimertinib in EGFR-mutated NSCLC.
e24178 Background: In advanced EGFR-mutated NSCLC, osimertinib is administered over prolonged periods, making patient-reported symptom burden a key determinant of quality of life and treatment sustainability. Clinician-reported safety assessments incompletely capture low-grade, cumulative, and patient-relevant toxicities. We hypothesized that longitudinal patient-reported outcomes (PROs) could identify clinically meaningful tolerance phenotypes with prognostic implications. Methods: Structured longitudinal PRO data from 94 patients treated with osimertinib were analyzed, covering 89 symptom domains with severity and timing. PROs were collected using a validated, web-based tool (Cureety), with high compliance and systematic weekly reporting throughout treatment. Symptoms were assessed based on prevalence, temporal relationship to drug exposure, and biological plausibility. Unsupervised hierarchical clustering identified tolerance phenotypes. Associations with dose modification and exploratory survival outcomes were evaluated. Results: Patients reported a substantial symptom burden, with a median of 8 symptoms per patient (range 0–32). Three distinct and clinically interpretable tolerance phenotypes were identified. The Early On-Target Toxicity Phenotype (≈33%) was characterized by early dermatologic and gastrointestinal toxicities (rash, diarrhea, mucositis) and the highest rate of dose modification (≈25–30%). Median progression free survival (PFS) and overall survival (OS) in this group were 12.5 months and 22.1 months, respectively. The Cumulative Burden Phenotype (≈30%) was dominated by persistent constitutional and neurocognitive symptoms (fatigue, anorexia, dizziness, cognitive complaints) emerging with prolonged exposure, and showed an unfavorable survival trend (median PFS 9.1 months, OS 16.8 months). The Clinically Silent Exposure Phenotype (≈37%) was characterized by minimal persistent symptoms and low rates of dose modification ( < 10%) and were associated with longer survival (median PFS 18.4 months, OS 34.6 months). Conclusions: PRO-based monitoring reveals distinct tolerance phenotypes under osimertinib with differential survival outcomes. These symptoms may reflect adequate systemic drug exposure rather than toxicity-driven treatment compromise. These findings support integrating longitudinal PRO monitoring into routine care and future trials to individualize dose management and follow-up strategies. Key patient-reported tolerance profiles and outcomes. Phenotype / Symptom Proportion (%) Median PFS (mo) Median OS (mo) Early on-target toxicity phenotype ~33 12.5 22.1 Cumulative burden phenotype ~30 9.1 16.8 Clinically silent exposure phenotype ~37 18.4 34.6
Efficacy and safety of tislelizumab and apatinib combined with hepatic arterial infusion chemotherapy for advanced intrahepatic cholangiocarcinoma: A single-arm, phase 2 study.
e16169 Background: Advanced intrahepatic cholangiocarcinoma (ICC) remains a highly aggressive malignancy with limited treatment options and poor prognosis. Systemic chemotherapy and immune therapies have shown modest efficacy, highlighting the need for novel combination strategies. This single-arm phase 2 study evaluated the efficacy and safety of tislelizumab (a PD-1 inhibitor) combined with apatinib (a VEGFR-2 inhibitor) and hepatic arterial infusion chemotherapy (HAIC) in patients with advanced ICC. Methods: Eligible patients with histologically confirmed advanced ICC were enrolled between Jan 2022 and Jun 2025. Treatment consisted of HAIC (oxaliplatin 130 mg/m²,5-Fu 400mg/ m², 5-Fu 1200mg/ m² via hepatic artery on day 1/2 each 3-week cycle), tislelizumab (200 mg intravenously every 3 weeks) and apatinib (250 mg orally daily). The primary endpoint was objective response rate (ORR) per RECIST v1.1, assessed by independent radiological review. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 17 patients were enrolled, with a median follow-up of 22 months. The confirmed ORR was 41.2% (95% CI: 18.4%-67.1%). The DCR was 88.3% (95% CI: 65.6%-98.5%). Median PFS was 8.8 months (95% CI: 4.33 - NA months), and the median OS was 17.6 months (95% CI: 15.0 - NA months). Notably, 3 of 17 patients (17.6%) subsequently underwent liver tumor resection with curative intent, achieving R0 resection. Eight patients (47.1%) had at least one any-grade treatment-related adverse event (TRAE); grade 3-4 TRAEs occurred in 3 patients (17.6%), with elevated transaminases (47.1%) being most common. No treatment-related deaths occurred. Conclusions: The combination of HAIC, tislelizumab and apatinib demonstrated promising efficacy with a manageable safety profile in advanced ICC, supporting further investigation in larger controlled trials.
Conditional survival following first-line treatment of MSS metastatic colorectal cancer: A pooled analysis of 12 randomized controlled trials.
e15565 Background: Metastatic colorectal cancer (mCRC) has a poor prognosis and is a major burden to patients and healthcare systems. In the last decades, the therapeutic landscape of mCRC has evolved, improving overall survival (OS). Conditional survival estimates prognosis among patients who already survived a defined period, which can guide individual risk assessment and treatment decisions in the course of disease. Analysis of conditional OS and progression-free survival (PFS) in a large cohort of mCRC patients receiving first-line systemic treatment is lacking. Methods: We analyzed data of mCRC patients from the safety analysis set of 12 randomized controlled trials. Patients with incomplete data, MSI-H patients and patients who received immune checkpoint inhibitors in first line treatment were excluded. OS was calculated from time of randomization or registration until death. PFS was calculated from time of randomization or registration until progression or death, whichever occurred first. Conditional survival was estimated among patients alive and/or progression-free at predefined landmarks (12, 24, and 36 months). Survival was assessed using the Kaplan-Meier method and Cox proportional hazard modeling. The Benjamini-Hochberg method was used to adjust for multiple testing. Results: 3,507 patients from the initial cohort met the inclusion criteria and were analyzed. Mean age was 61.5 years and 64.1% were male. Median follow-up was 50.7 months. Details of conditional survival estimates of patients in our cohort are summarized in table 1. Interestingly, the “remaining” OS ranged from 20-27 months, irrespective of the landmark analyzed. In patients with PFS > 24 months, only history of local or surgical treatment of metastases in the first 24 months (HR 0.31, p < 0.001) and only one organ initially involved with metastases (HR 0.54, p = 0.022) were significantly associated with ongoing conditional OS. Conclusions: Conditional OS of mCRC patients alive at predefined OS landmarks remained stable with increasing OS time. Furthermore, conditional OS and PFS improved substantially in patients with PFS > 24 months after first-line treatment. In this small, but significant fraction of patients, initial local or surgical treatment might be the key factor of long survival. OS/PFS landmark Proportion surviving (OS) [%] Proportion surviving (PFS) [%] median cOS (OS-conditioned) median cOS (PFS-conditioned) median cPFS (PFS-conditioned) 0 100.0 100.0 27.29(26.16 - 28.03) 27.29(26.16 - 28.03) 10.53(10.26 - 10.81) 12 83.2 42.4 19.68(18.77 - 21.16) 32.29(30.6 - 34.97) 6.11(5.65 - 6.71) 24 55.6 13.4 19.65(18.29 - 21.29) 81.38(47.1 - NE) 18.97(15.35 - 25.53) 36 36.2 7.9 20.97(19.19 - 23.93) 69.38(NE - NE) 32.06(31.3 - NE) cOS, conditional OS; cPFS, conditional PFS; NE, not estimable. Time is reported in months. 95% confidence intervals are indicated in brackets.
Five-decade national trends and forecasting of brain tumor mortality among older adults in the United States, 1968–2035.
e14051 Background: Malignant brain tumors remain a major contributor to neurologic mortality in older adults. Despite advances in neurosurgery, radiation therapy, and systemic treatments, contemporary population-level evaluations of long-term mortality trajectories are limited. Characterizing national trends and future burden is critical for healthcare planning and addressing emerging disparities. We evaluated five-decade mortality patterns and projected future trends of malignant brain tumor–related deaths among U.S. adults aged ≥65 years. Methods: We conducted a retrospective population-based analysis using the CDC Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1968–2023. Deaths attributed to malignant brain tumors were identified using ICD-8 (191), ICD-9 (191), and ICD-10 (C71) codes. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated and stratified by age group, sex, race/ethnicity, U.S. census region, state, and urban–rural classification. Temporal trends were assessed using Joinpoint regression to estimate average annual percent change (AAPC) with 95% confidence intervals (CI). Mortality projections through 2035 were generated using autoregressive integrated moving average (ARIMA) time-series models with diagnostic validation. Results: Between 1968 and 2023, 311,680 malignant brain tumor–related deaths occurred among adults aged ≥65 years. The overall mean AAMR was 15.2 per 100,000, increasing steadily and peaking at 18.3 in 2021 (AAPC: 1.90%; 95% CI: 1.6–2.2). Forecast modeling projected continued elevation in mortality burden, with AAMR reaching 18.06 by 2035 (p<0.00001), supported by satisfactory model performance (ADF p=0.63; Ljung–Box p=0.30). Although males demonstrated higher overall mortality compared with females (mean AAMR: 18.7 vs 12.6), mortality acceleration was greater among females (AAPC: 1.94% vs 1.82%). The 65–74-year age group accounted for the highest absolute burden (167,418 deaths). Racial disparities were observed, with non-Hispanic Black individuals exhibiting the steepest mortality increase (AAPC: 2.70%), followed by White individuals (AAPC: 1.96%). Regionally, the South demonstrated the fastest rising trend (AAPC: 2.19%), while Vermont exhibited the highest state-level mortality burden (AAMR: 23.5 per 100,000). Conclusions: Over the past five decades, malignant brain tumor mortality among older U.S. adults has risen significantly and is projected to remain elevated through 2035. Accelerating trends among women, Black populations, and Southern regions highlight widening disparities in neuro-oncologic outcomes. These findings underscore the urgent need for targeted early detection strategies, equitable access to specialized neuro-oncology care, and resource allocation planning to address the growing aging-related brain tumor burden.
Baseline prevalence of lung cancer screening and covariates among women undergoing breast cancer screening in Missouri.
e22562 Background: We sought to evaluate lung cancer screening (LCS) uptake and determine factors associated with LCS among women participating in a highly-attended breast cancer screening (BCS) program in Missouri. Methods: We conducted a retrospective cohort study using electronic health record data (2019 to 2025) of women aged 50–80 years with documented smoking history undergoing BCS at Barnes-Jewish West County (BJWCH), serving ~4,500 women, and Christian Hospital (CH), serving ~9,000 women in Missouri. LCS eligibility was assessed based on current smoking status, > 20 smoking pack-years, and/or < 15 years since quitting among former smokers. We evaluated LCS uptake and conducted multivariable analyses to explore demographic, behavioral, and area-level characteristics associated with LCS eligibility and uptake. Results: A total of 8,709 women had ever smoked; 2,530 from BJWCH and 6,179 from CH. Most women were non-Hispanic Black (52.4%) and non-Hispanic White (45.2%), with CH serving mostly Blacks (67.6%) and BJWCH primarily White (80.6%). At BJWCH, 30% of women, and at CH, 34.6% had undergone LCS. Only 37% of patients had documented pack-years. Documentation of pack-years was more likely among current smokers (AOR = 1.89; 95% CI: 1.69–2.11; p < 0.001) and was associated with higher likelihood of LCS (AOR = 3.27; 95% CI: 2.97–3.60; p < 0.0001). LCS uptake among those with documented pack-years was 43.8% (N = 411) and 54.6% (N = 1,251) at BJWCH and CH, respectively. Current smoking status was associated with higher LCS uptake (AOR = 2.05, 95% CI: 1.82–2.31, p < 0.001) compared to former smoking status. A dose–response relationship was observed with pack-years and LCS (table 1). Residence in higher neighborhood deprivation was associated with a higher likelihood of LCS (table 1). Effect modification by race/ ethnicity attenuated the positive association between smoking > 40 pack-years and LCS among non-Hispanic Blacks (AOR = 2.03 (95% CI: 1.02–4.03), p = 0.036). Conclusions: LCS uptake among women remains low, and poor documentation of pack-years undermines accurate LCS eligibility determination. LCS uptake was lower among those with former smoking status, and the attenuated association between high pack-years and LCS among non-Hispanic Blacks suggests potential disparities in translating risk to LCS. System-level efforts to strengthen pack-year documentation and LCS-eligibility assessment, particularly among former smokers, could expand uptake of LCS. Variable Reference group AOR 95% CI p-value Pack-year documentation Documented vs not 3.27 2.97–3.60 <0.0001 Smoking status Current vs former 2.05 1.82–2.31 <0.001 Pack-years 20–29 pack years 30–39 1.7 1.27–2.28 <0.001 ≥40 2.79 2.11–3.68 <0.001 Undocumented 0.19 0.16–0.23 <0.001 Area deprivation Category 1 Category 2 1.12 0.87 – 1.45 0.371 Category 3 1.33 1.04–1.69 0.023 Category 4 1.59 1.26–2.00 <0.001
Advancing treatment of low-grade upper tract urothelial carcinoma (LG UTUC) with padeliporfin vascular-targeted photodynamic therapy (VTP): The ENLIGHTED phase 3 trial.
TPS4643 Background: Padeliporfin VTP is a drug-led combination therapy consisting of IV Padeliporfin activated by a low-power near-infrared (753 nm) laser–fiber system. A non-contact cylindrical fiber positioned near the tumor provides circumferential illumination, inducing vascular occlusion and coagulative tumor necrosis while preserving tissue structure. Safety and efficacy were shown in a Phase 1 UTUC study (NCT03617003). We report emerging efficacy, durability, and safety from the ENLIGHTED Phase 3 trial in LG UTUC (NCT04620239). Methods: ENLIGHTED is an open-label Phase 3 study conducted in the US, EU, and Israel, evaluating the efficacy, durability, and safety of padeliporfin VTP in LG UTUC. Eligible patients (pts) may have new or recurrent disease, be treatment-naïve or previously treated, and have up to two biopsy-confirmed LG lesions (5–15 mm kidney or 5–20 mm ureter) without high-grade cells on instrumented cytology. VTP is performed via retrograde upper tract endoscopy under anesthesia and low-light conditions. Padeliporfin is administered IV, and an optical fiber with a 20–40 mm diffuser is positioned near the tumor through the scope, followed by 10 minutes of laser illumination. Treatment consists of an Induction Treatment Phase (ITP) of 1–3 VTP sessions at 4-week intervals until complete response (CR) or treatment failure at Primary Response Evaluation (PRE). Pts achieving CR enter a 12-month Maintenance Treatment Phase (MTP) with quarterly endoscopic surveillance and retreatment for treatable recurrences, followed by long-term follow-up up to 48 months. The primary endpoint is CR at PRE (28 ± 3 days post last ITP treatment), defined by absence of visible tumor on endoscopy and negative instrumented cytology. A total of 100 pts are to be enrolled. As of January 19, 2026, 78 pts were enrolled and 63 completed ITP. Response rates were: CR 73.0%, PR 17.7%, DR 3.2%, PD 4.8%, and stable disease 1.6%. Among pts with CR at PRE, 39.5% had completed MTP by data cutoff, with 88.2% maintaining CR in the treated area (TA) for ≥12 mos. Median Duration of Response in the TA was not reached and is ≥23.9 mos. Most pts remains in MTP or follow-up. The most common treatment-emergent adverse events were hematuria (10.6%), flank pain (8.6%), nausea (5.5%), procedural pain (4.5%), abdominal pain (4.1%), dysuria (4.1%), vomiting (3.4%), and fatigue (3.1%), all Grade 1–2 with a median duration of 5 days. 23 serious adverse events (7.7%) were reported, mostly unrelated to treatment. One Grade 3 SAE (renal colic related to VTP) resolved within 2 days. Padeliporfin VTP demonstrates favorable preliminary efficacy, durable responses, and a safety profile consistent with prior experience. Enrollment is ongoing, and final outcomes are anticipated to support regulatory approval of an organ-preserving therapy for LG UTUC. Clinical trial information: NCT04620239 .
Clinicogenomic characteristics associated with non-durable response to first-line immunotherapy among advanced lung squamous cell carcinoma with PD-L1 ≥ 50%.
e20614 Background: While immune checkpoint inhibitors (ICIs) are a cornerstone of therapy in advanced lung squamous cell carcinoma (LSqCC) with PD-L1≥50%, clinical outcomes are variable and additional biomarkers to predict response to ICIs are poorly defined. We compared clinical and genomic characteristics of individuals with durable response (DR) and non-durable response (NDR) to ICIs. Methods: We conducted a retrospective analysis of individuals with advanced LSqCC and PD-L1 TPS ≥50% treated with frontline ICI-based therapy at Indiana University Health System from January 1, 2018 - June 30, 2025. Demographics, clinical features associated with poor response to ICIs, and next-generation sequencing data were collected using electronic medical records. Response was assessed using standardized real-world criteria. Median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. DR and NDR were defined as a PFS ≥ and <6 months, respectively. Variables were compared using Wilcoxon/χ²/Fisher’s exact tests. Results: We identified 646 individuals with LSqCC of whom 41 were eligible for analysis. 19 (46%) had a NDR with a mean age of 68 (vs. 66 for DR; p=0.44). 63% were male (vs. 59%; p=0.79), 79% were white (vs. 73%; p> 0.99), and 95% were current/former smokers (vs. 96%; p>0.99). Individuals with NDR had lower baseline hemoglobins but were otherwise similar to those with DR, Table. ICI monotherapy was more common among those with NDR (74% vs. 26%), while chemo-ICI was more frequently used in those with DR (73% vs. 26%, p< 0.01). As expected, response rates (21% vs. 86%; p <0.01), PFS (2.9 vs. 10.8 mo; p< 0.01), and OS (9.4 vs. 19.6 mo; p=0.03) were significantly lower among those with NDR. KRAS alterations were more frequent among those with DR (24% vs. 5%; p =0.19), while CDKN2A and CDKN2B alterations were significantly more common among those with NDR (63% vs. 19% and 21% vs. 0%, p < 0.01). Conclusions: In our cohort, 46% of advanced LSqCC with PD-L1≥50% had a NDR to frontline ICIs. While clinical factors were comparable, chemo-ICI use was more common among DR, suggesting the addition of chemotherapy to ICIs may result in improved outcomes even with PD-L1≥50% LSqCC. The presence of CDKN2A/B alterations among those with NDR suggests a potential association with poor ICI response that warrants further investigation and highlights the role of genomic profiling to identify biomarkers beyond PD-L1 for treatment selection in LSqCC. Variable NDR n=19 (46.3%) DR n=22 (53.7%) P Stage IV 8 (42.1) 11 (50.0) 0.475 Metastasis Brain/Bone/Liver 7 (36.8) 10 (45.5) 0.922 BMI≥25 14 (73.7) 15 (68.2) 0.848 ECOG ≥2 2 (10.5) 3 (13.6) >0.999 Immunosuppression 1 (5.3) 5 (22.7) 0.184 Hb – mean (range) 11.3 (7.3 – 16.7) 12.5 (9.7 – 15.8) 0.047 ANC/ALC ratio ≥3 11 (57.9) 14 (63.6) 0.893 PD-L1 ≥90% 7 (36.8) 11 (50.0) 0.621
Botensilimab (BOT) ± balstilimab (BAL) in patients (pts) with advanced cutaneous melanoma (cMEL) refractory/resistant (R/R) to anti–PD-(L)1 ± CTLA-4: A phase 2 trial.
9543 Background: Pts with advanced cMEL R/R to PD-(L)1–based therapy, including PD-(L)1+CTLA-4, have few treatment options. BOT (Fc-enhanced anti–CTLA-4) augments T-cell priming, depletes Tregs, and activates antigen-presenting cells to overcome immune checkpoint inhibitor (ICI) resistance. BOT ± BAL (anti–PD-1) has shown activity in ICI-R/R and cold tumors. Methods: The open-label, global phase 2 C-800-23 trial (NCT05529316) enrolled pts with cMEL (stage III unresectable or IV) R/R to prior anti–PD-(L)1 ± CTLA-4. Part 1: randomized 1:1 to BOT 50 mg or 150 mg every 3 weeks (Q3W; up to 4 doses). Part 2: BOT 75 mg Q3W (up to 4 doses) plus BAL 450 mg Q3W (up to 2 years). Endpoints included confirmed objective response rate (ORR; primary; RECIST 1.1), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety. Clinical benefit rate (CBR) was complete or partial response or stable disease for ≥24 weeks. Results: As of Dec 13, 2025, 138 pts received BOT monotherapy (median follow-up, 12.3 mo; range, 0.2–35+) and 36 pts received BOT+BAL (median follow-up, 13.8 mo; range, 2–26+). Overall, 51% had stage M1c or M1d disease, 29% had BRAF mutant disease, and 39% had LDH >ULN. In pts R/R to anti–PD-(L)1, 72% (60/83 with pre-trial data available) had primary resistance (best overall response of progressive disease [PD] or PD ≤6 mo from most recent course of respective ICI type). In pts R/R to anti–PD-(L)1+CTLA-4, 69% (61/88) had primary PD-(L)1 resistance and 69% (60/87) had primary CTLA-4 resistance. With BOT+BAL, ORR was 22% (95% CI, 10–39), CBR was 33% (95% CI, 19–51), median DOR was not reached (NR; 95% CI, 4.17–NR), 12-mo PFS was 29% (95% CI, 15–44), and median OS was 16.6 mo (95% CI, 9.1–NR; 24-mo OS, 46%; 95% CI, 29–61). ORR with BOT+BAL was numerically higher in PD-(L)1+CTLA-4 R/R pts (29%, 4/14; 95% CI, 8–58; 3/4 responders had primary ICI resistance) vs PD-(L)1–only R/R pts (18%, 4/22; 95% CI, 5–40; all responders had primary ICI resistance). With BOT alone, ORR was 6% (95% CI, 3–11), CBR was 14% (95% CI, 9–21), 12-mo PFS was 7% (95% CI, 3–13), and median OS was 12.9 mo (95% CI, 9.7–16.2; 24-mo OS, 28%; 95% CI, 20–36). Responses were irrespective of Fcγ receptor genotype. Treatment-related adverse events occurred in 81% (grade ≥3, 30%) with BOT alone and 94% (grade ≥3, 36%) with BOT+BAL; most common was diarrhea (BOT 33%; BOT+BAL 42%). One possibly treatment-related death was reported with BOT monotherapy (immune-mediated enterocolitis). No new safety signals occurred. Conclusions: In this ICI-R/R cMEL population enriched with primary ICI-resistant pts, BOT+BAL showed durable responses, encouraging survival, and a stronger signal in pts who had prior conventional anti–CTLA-4. BOT monotherapy also showed activity. This supports a differentiated mechanism for BOT and continued development of BOT+BAL, including for pts with dual ICI-R/R cMEL. Clinical trial information: NCT05529316 .
Neoadjuvant therapy for head and neck squamous cell carcinoma based on hyperprogression genotyping: Cetuximab beta combined with chemotherapy with or without camrelizumab.
TPS6139 Background: Surgery remains the preferred treatment option for locally advanced head and neck squamous cell carcinoma (LA HNSCC). However, its efficacy is still unsatisfactory, with local recurrence and distant metastasis rates as high as 20% and a 5-year survival rate of only about 50%. Immune checkpoint inhibitors (ICIs) have achieved success in recurrent/metastatic HNSCC (R/M HNSCC), laying the foundation for the application of immunotherapy in earlier-stage patients. Cetuximab, an anti-Epidermal Growth Factor Receptor (EGFR) antibody, is a standard treatment for both LA HNSCC and R/M HNSCC. Patients who experience Hyperprogressive Disease (HPD) have a poor prognosis, and various genetic mutations have been shown to predict the occurrence of HPD. Methods: This study was designed as a prospective, open label, multicenter, phase II trial (ChiCTR2500108701), and the primary endpoint was the postoperative pathological complete response (pCR) rate. The secondary endpoints included the objective response rate (ORR), major pathological response (MPR) rate, 1-year and 2-year event-free survival (EFS) rates, and 2-year overall survival (OS) rate. Eligible patients (pts) were over 18 years old with histologically or cytologically confirmed SCCHN (excluding nasopharyngeal carcinoma); had T1N2-3M0, T2N1-3M0, or T3/T4aNanyM0, according to the 8th Edition of the American Joint Committee on Cancer (AJCC) staging guidelines; had resectability of the tumor was evaluated by a head and neck surgeon; had no previous local and systemic treatment for SCCHN; had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; had measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST 1.1). All enrolled 40 pts received whole exome sequencing (WES), and were assigned to Cohort A (n=25, HPD-gene-negative) and Cohort B (n=15, HPD-gene-positive), respectively. All treatment was administered intravenously in 21-day cycles. Patients in Cohort A were given albumin-bound paclitaxel (260 mg/m², d1), cisplatin (25 mg/m², d1-d3), camrelizumab (200 mg, d1) and cetuximab (250 mg/m², d1;500 mg/m², d8). Patients who successfully completed 2~4 cycles of neoadjuvant treatment returned for surgical intervention 28~42 Endpoints days after the last cycle, and adjuvant radiotherapy was administered followed by 2~4 cycles of camrelizumab (200 mg, d1) and cetuximab (250 mg/m², d1;500 mg/m², d8) as adjuvant treatment.Cohort B received the same treatment regimen as Cohort A, excluding camrelizumab. Clinical trial information: ChiCTR2500108701.